A Descriptive Study of Allergen-Specific Ige Serological Tests for Canine Atopic Dermatitis in Thailand Suttiwee Chermprapai1,2 and Naris Thengchaisri1*

Chermprapai and Thengchaisri BMC Veterinary Research (2020) 16:475 https://doi.org/10.1186/s12917-020-02684-x

RESEARCH ARTICLE Open Access A descriptive study of allergen-specific IgE serological tests for canine atopic dermatitis in Thailand Suttiwee Chermprapai1,2 and Naris Thengchaisri1*

Abstract Background: This study describes the usefulness of allergen-specific Immunoglobulin E (IgE) serology (ASIS) for identifying allergens in dogs with atopic dermatitis. ASIS tests were conducted in 23 dogs diagnosed with atopic dermatitis for indoor allergens (yeast and mites), outdoor allergens (grass pollen, weed pollen, and tree pollen), and fleas. The relationship among positive ASIS tests were determined using Pearson’s correlation coefficient (r). Results: Of the atopic dogs, 26.09%, 4.35%, and 47.83% had positive ASIS tests for only indoor allergens, only outdoor allergens, and both indoor and outdoor allergens, respectively. The prevalence of positive ASIS tests was highest for mites (69.57%) and did not differ between indoor and outdoor allergens by age, breed, or sex. The prevalence of positive ASIS tests for indoor allergens during the rainy season (84.21%) was significantly higher than during winter (25.00%, P-value = 0.030). The correlation coefficient of the ASIS results among the outdoor allergens indicated a strong correlation between grass and tree pollen (r = 0.840, P-value < 0.01), grass and weed pollen (r = 0.812, P-value < 0.01), and tree and weed pollen (r = 0.714, P-value < 0.01). The correlation coefficient of the ASIS results of D. farinae indicated a strong correlation with A. siro (r = 0.951, P-value < 0.01) and a moderate correlation with B. tropicalis (r = 0.656, P-value < 0.01) and T. putrescentie (r = 0.672, P-value < 0.01). Conclusions: ASIS tests are useful in screening for multiple allergens in dogs with atopic dermatitis. Dust mites are an important source of indoor allergens and may be responsible for a higher titer of IgE antibodies against indoor allergens during the rainy season. Keywords: Allergy, Allergen-specific IgE test, Atopic dermatitis, Dogs, House dust mite

Background recent development of allergen-specific IgE serology Canine atopic dermatitis (CAD) is a chronic multifactorial (ASIS) have contributed to the rapid identification of com- inflammatory and pruritic allergic skin disease with dis- mon indoor/outdoor allergens among dogs with atopic tinctive clinical features [1]. The pathogenesis of CAD has dermatitis (AD) [6]. The usefulness of ASIS tests in clin- been linked to skin barrier dysfunction, immune responses ical settings compared with intradermal skin tests (IDTs) to indoor and outdoor allergens, and complicated infec- for specifying the causal allergens remains controversial tions [2–4]. Elevation of serum Immunoglobulin E (IgE) is [7]. IDTs are commonly used in clinical practice, even commonly found in CAD and is believed to be one of the though the testing may lead to patient discomfort as well main mediators for hypersensitivity reactions [5]. The as anaphylactic reactions [5]. ASIS tests cause less pain for canine patients without the need to shave the dog’shair * Correspondence: [email protected] and use sedative agents [7]. The application of ASIS tests 1Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, 10900 Bangkok, Thailand in atopic dogs provides a good solution for conditioned Full list of author information is available at the end of the article patients.

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Different types of allergens can be synchronously in- 47.83%, respectively (Fig. 1). Of the atopic dogs, 21.74% vestigated within the same test [8]. The most common had negative ASIS test results. The prevalence of ASIS allergens in CAD are house dust mites, storage mites, tests positive for specific allergens from highest to lowest pollen, molds, and epidermal allergens; the allergens in- was as follows: mites (69.57%), weed pollen (43.48%), grass volved can vary by geographic location [8]. Selecting pollen (34.78%), tree pollen (30.43%), yeast (30.43%), and relevant allergens in a patient’s local region helps in- fleas (0.00%). The prevalence of positive ASIS results for crease the chance of finding significant test results [7]. the allergens examined is shown in Table 1. Among in- Research investigating the usefulness of allergen identifi- door allergens, the prevalence of house dust mites (D. fari- cation in atopic dogs in Thailand is limited and has been nae = 56.52%) and storage mites (T. prutescentie =56.52%; performed only by IDT not ASIS [9]. Previous studies A. siro =52.17%; B. tropicalis = 30.43%) was found to be reported the influence of breed on atopic dogs and links highest. Among outdoor allergens, grass pollen was most to possible genetic-related problems [10]. Findings on prevalent (17.39–30.43%). The prevalence of positive ASIS the influence of age, body size, and sex among these tests for indoor and outdoor allergens in atopic dogs did dogs have been inconsistent [11–13]. It is possible that not differ according to age, breed, and sex (Table 2). The seasonal influence may also affect the results of ASIS number and percentage of atopic dogs with a positive or tests [11]. Thailand is located in a tropical region, South- negative ASIS score for the 6 types of allergens are pro- east Asia, and has three seasons: summer, rainy season, vided in Table 3. These results indicated that mite and and winter; which differs from temperate and subpolar yeast were the predominant indoor allergens, respectively. regions that have four seasons: summer, spring, autumn, Weed pollen, tree pollen and grass pollen were the most and winter [14, 15]. Most earlier studies observed that dominant outdoor allergens, respectively. The share of dogs with AD tend to develop clinically allergic re- positive ASIS tests among atopic dogs for indoor allergens sponses in the spring and summer [16–18]. during the rainy season (84.21%) was significantly higher The objective of the present study was to evaluate the than that found during the winter season (25.00%, P- usefulness of ASIS tests for identifying specific indoor and value = 0.030; Table 4). The share of positive ASIS tests outdoor allergens in atopic dogs. The relationship between for outdoor allergens during the rainy season (52.63%) positive ASIS results among different allergens, as well as was comparable to that found during the winter season the influence of climate conditions, was compared. (50.00%, P-value = 0.127; Table 4). The correlation coefficient of the ASIS results among the Results outdoor allergens indicated a strong correlation between The percentage of atopic dogs with ASIS tests positive for grass pollen and tree pollen (r = 0.840, P-value < 0.01), grass only indoor allergens (yeast and mites), only outdoor aller- pollen and weed pollen (r = 0.812, P-value < 0.01), and tree gens (grass pollen, weed pollen, and tree pollen), and both pollen and weed pollen (r = 0.714, P-value < 0.01; Table 5). indoor and outdoor allergens was 26.09%, 4.35%, and The correlation coefficient of the ASIS results of D. farinae

Fig. 1 Summarized results of allergen-specific IgE serological (ASIS) tests in atopic dogs classified by indoor and outdoor allergens Chermprapai and Thengchaisri BMC Veterinary Research (2020) 16:475 Page 3 of 7

Table 1 Percentage and number of atopic dogs with positive results to different allergens according to the allergen-specific IgE serological (ASIS) tests Number Name of allergen Group Number of positive IgE (n = 23) Percentage of positive IgE 1 Malassezia pachydermatis 1 7 30.43 2 Flea saliva 2 0 0.00 3 Dermatophagoides farinae 3 13 56.52 4 Blomia tropicalis 3 7 30.43 5 Tyrophagus putrescentiae 4 13 56.52 6 Acarus siro 4 12 52.17 7 Bermuda grass (Cynodon dactylon) 5 5 21.74 8 Bahia grass (Paspalum notatum) 5 4 17.39 9 Johnson grass (Sorghum halepense) 5 4 17.39 10 Meadow fescue (Festuca pratensis) 5 7 30.43 11 Timothy grass (Phleum pratense) 5 5 21.74 12 Red/sheep sorrel (Rumex acetosella) 5 6 26.09 13 Lamb’s quarter (Chenopodium album) 5 4 17.39 14 Russian thistle (Salsola kali) 6 5 21.74 15 Careless weed (Amaranthus hybridus) 6 5 21.74 16 Cocklebur (Xanthium strumarium) 6 3 13.04 17 Marsh elder (Cyclachaena xanthiifolia) 6 3 13.04 18 Common and giant ragweed 6 5 21.74 (Ambrosia artemisiifolia and A. trifida) 19 English plantain (Plantago lanceolate) 6 5 21.74 20 Mugwort (Artemisia vulgaris) 6 2 8.70 21 Paperbark tree (Maleleuca quinquenervia) 7 2 8.70 22 White mulberry (Morus alba) 7 4 17.39 23 Queen and oil palms 7 5 21.74 (Arecastrum romanzoffianum and Elaeis guineensis) 24 White oak (Quercus alba) 7 3 13.04 Group category 1: Yeast, 2: Flea, 3: House dust mite, 4: Storage mite, 5: Grass pollen, 6: Weed pollen, 7: Tree pollen

(Table 5) indicated a strong correlation with A. siro (r = Unlike human medicine, for which several atopic 0.951, P-value < 0.01) and a moderate correlation with B. tro- dermatitis-related genes have been studied [19, 20], only picalis (r = 0.656, P-value < 0.01) and T. putrescentie (r = the gene related to IgE production has received attention 0.672, P-value < 0.01). in veterinary medicine, and a limited correlation has been observed between clinical atopic dermatitis development and IgE levels or other genes [21–24]. The up- Discussion dated practical guidelines to diagnose CAD include In the present study, ASIS tests were performed for dogs ruling out other pruritic skin diseases, interpreting the with atopic dermatitis across 24 allergens. Our findings clinical features as described as Favrot’s criteria, and indicate the important role of indoor allergens over out- identifying causal allergens either through IDTs or ASIS door allergens. House dust mites and storage mites were testing [7]. Although ASIS can have poorer specificity the predominant allergens among the atopic dogs. We and lower positive predictive value compared with IDTs, also identified that during the raining season, indoor al- ASIS tests provide several advantages over IDTs, such as lergens were the main source of allergens. It should be (1) no patient risk related to sedation or of anaphylactic noted that the positive ASIS results of the outdoor aller- reactions, (2) convenience (no hair clipping, no re- gens (grass pollen, weed pollen, and tree pollen) were straint), (3) a lower likelihood of influence related to highly correlated. Positive ASIS results for house dust prior or current drug therapy, and (4) shorter duration mite allergens were moderately to highly associated with (easily done in a minute) [25]. Identifying allergens by positive ASIS results for storage mites. ASIS testing is favorable when patients have certain Chermprapai and Thengchaisri BMC Veterinary Research (2020) 16:475 Page 4 of 7

Table 2 Allergen-specific IgE serological (ASIS) test results in atopic dogs by age, sex, and breed Category Subtype No. positive No. negative % positive P-value Indoor IgE allergens Age group Young (1–3 years) 7 1 87.50 — Adult (> 3 years) 10 5 67.67 0.369 Breed Small 4 2 67.67 — Medium 8 3 72.73 1.000 Large 5 1 83.33 1.000 Sex Male 7 4 63.64 — Female 10 2 83.33 0.371 Outdoor IgE allergens Age group Young (1–3 years) 5 3 62.50 — Adult (> 3 years) 7 8 46.67 0.667 Breed Small 2 4 33.33 — Medium 8 3 72.73 0.162 Large 2 4 33.33 1.000 Sex Male 4 7 36.36 — Female 8 4 66.67 0.220

limitations that preclude the use of an IDTs, like most of patented Fc-ε receptor testing method (Allercept), which the patients enrolled in this study. In the current study, can provide a low chance of cross-reactivity of positive there were some dogs with clinical features of AD but results [30]. However, the cross-reactivity in the same an undetectable IgE response to allergens; this can be group of allergens, such as house dust and storage mites, explained by the possible confounding problems of remains and cannot be ruled out [31]. Another study recruiting patients with atopic-like dermatitis or by the demonstrated that the prevalence of positive ASIS re- fact that the ASIS testing cannot detect the presence of sults using the high-affinity FcεRIα was similar or even cutaneous mast cells with reaginic antibodies present on better than the results of IDTs [32]. It is noteworthy that the mast cells [25, 26]. the correlation between the results of ASIS tests and It has been described previously that ASIS tests mea- IDTs possibly ranged from weak to strong depending on sured by enzyme-linked immunosorbent assay (ELISA) numerous factors, including standardization of allergens, can be analyzed by using mono- or polyclonal antibodies testing technique and laboratory conditions, or individ- or the high-affinity Fc epsilon receptor alpha chain pro- ual factors [33–35]. Positive results of IDTs and ASIS tein (FcεRIα), and positive results have varied among tests should be compared with caution. The proper se- these assays [27, 28]. Although the chance of cross- lection of diagnostic tools helps improve the sensitivity reactivity between IgE and IgG has been discussed [29], and the specificity of the test and thus the ability to reli- the serum samples of this study were analyzed by the ably identify patients’ clinically relevant allergens.

Table 3 Percentage and number of atopic dogs according to allergen specific IgE serological (ASIS) scores among different groups of allergens (yeast, mites, grass pollen, weed pollen, and tree pollen) Allergy group No. of dogs with No. of dogs with % positive P-value IgE score of 2–4 IgE score of 0–1 Yeast 7 16 30.43 — Flea 0 23 0.00 0.004 Mite 16 7 69.57 0.008 Grass pollen 8 15 34.78 0.753 Weed pollen 10 13 43.48 0.360 Tree pollen 7 16 30.43 1.000 Overall 18 5 78.26 0.003 Chermprapai and Thengchaisri BMC Veterinary Research (2020) 16:475 Page 5 of 7

Table 4 Seasonal effects on the results of allergen-specific IgE serological (ASIS) tests in atopic dogs Category Season No. positive No. negative % positive P-value Indoor allergens Rainy 16 3 84.21 — Winter 1 3 25.00 0.030 Outdoor allergens Rainy 10 9 52.63 — Winter 2 2 50.00 0.127 Both indoor and outdoor allergens Rainy 16 3 84.21 — Winter 2 2 50.00 0.064

Performing both an IDTs and ASIS testing can provide mites. The effect of seasonality on CAD development better outcomes with which to interpret an allergic re- should be further studied and include all the seasons in- sponse to tested allergens [36]. volved in the studied region. The clinical signs of CAD vary depending on several fac- The limitations of the present study include the cross- tors, including age of onset, breed, sex, anatomical site, reactivity, the seasonality effects, and the downsides of type of skin lesion, and seasonality [11]. Seasonality varies ASIS testing mentioned earlier, as well as the sample with respect to geographic location and relates to environ- size. No significant differences in positive ASIS results mental allergens [11]. Spring and summer have been most were observed for indoor and outdoor allergens based commonly described as related to the development and on age, breed, or sex. Given the retrospective nature of progression of allergic responses [16, 17]. Thailand is lo- the present study, we did not have cases with flare-up cated in Southeast Asia and has three seasons: summer, symptoms in summer during the period of the current the rainy season, and winter [15]. In our study, most of study for ASIS testing. More studies can be performed the patients’ serum samples were taken in the rainy and to identify the possible risks associated with the raining winter seasons with regard to the clinical presentation. It season resulting in the flare-up symptoms of the atopic was found that during the rainy season, indoor allergens dogs. It is possible that the sample size used in the were the main source of the allergens compared with the present study may be limited for identifying difference in outdoor allergens. House dust mites, the major indoor al- positive ASIS based on age, breed, or sex. Although lergen related to atopic dermatitis, prefer tropical and sub- none of the atopic dogs enrolled in this study had posi- tropical climates with relatively high humidity [37, 38]. tive ASIS results for flea antigens, this finding is fairly in When rainfall is heavy during the rainy season in agreement with earlier studies that found only a low Thailand, owners likely keep their animals indoors more prevalence of positive results for flea antigens [12, 39]. often, which may lead to increased exposure to house dust Improved population sampling and/or increased sample size of the study may have provided a more rigid conclu- Table 5 Pearson’s correlation coefficient (r) among groups of sion about serology testing for dermatitis related to flea indoor allergen (A. siro, B. tropicalis, D. farinae, T. putrescentie)or allergies as well as multivariate analysis of the factors as- outdoor allergens (yeast, mites, grass pollen, weed pollen, and sociated with CAD. tree pollen) in atopic dogs based on allergen-specific IgE serological (ASIS) tests Conclusions Indoor IgE allergens Multiallergen screening using ASIS tests revealed that Mite allergen Acarus siro Blomia D. farinae house dust mites and weed pollen are the most import- tropicalis ant sources of allergens in Thailand. The present find- Tyrophagus 0.789** 0.616** 0.672** ings indicated that during the rainy season, atopic dogs putrescentie may experience a higher titer of IgE antibodies against Acarus siro — 0.716** 0.951** indoor allergens. Cross-reactivities from ASIS tests likely Blomia tropicalis —— 0.656** occurred among dust mite allergens as well as different Outdoor IgE allergens types of pollen. ASIS testing serves the purpose of identifying allergens that may be included in the treatment. Allergen group Grass Weed pollen Tree Yeast pollen pollen The application of ASIS tests in atopic dogs provides a good solution for conditioned patients. Mite 0.288 0.305 0.288 0.308 — Grass pollen 0.812** 0.840** 0.205 Methods Weed pollen —— 0.714** 0.346 Animals Tree pollen —— —0.140 This study was approved by the Kasetsart University In- ** Indicates a P-value of <0.01 stitutional Animal Care and Use Committee (ACKU63- Chermprapai and Thengchaisri BMC Veterinary Research (2020) 16:475 Page 6 of 7

VET-044) and by the Ethical Review Board of the Office reaction, 1 = a light nonspecific reaction, 2 = a weak posi- of National Research Council of Thailand (NRCT license tive reaction, 3 = a moderate positive reaction, and 4 = a No. U1-08491-2562). Twenty-three client-owned dogs strong positive reaction. Reactions of greater than or equal with atopic dermatitis (12 females and 11 males, median to 2 were considered positive ASIS test results. age of 4.3 ± 4.0 years) of different breeds that visited the Dermatology Unit at Kasetsart University Veterinary Statistical analysis Teaching Hospital from 2017 to 2019 were included. The sample size was calculated using freely downloadable The dog owners were informed and educated about the software G*Power3.1 (Faul, Erdfelder, Lang and Buchner, practical approach of pruritic problem. The dogs met 2007) to detect a difference using an exact test with Favrot’s diagnostic criteria for atopic dermatitis, and alpha = 0.05 (two-tailed test), beta = 0.9, and an effect size other pruritic skin diseases were ruled out by direct of 0.25. The data were analyzed using STATA12 (Stata- examination of the ectoparasites, coat brushing, skin Corp, College Station, Texas, USA) and GraphPad Prism scrapings, and regular use of antiparasitic control [7]. In- Version 6 (GraphPad Software, San Diego, California, fection and inflammation caused by bacteria, fungi, and/ USA). The prevalence of ASIS results for different aller- or yeast were ruled out by skin cytology. Adverse food gens, as well as the prevalence of ASIS results acquired reaction was ruled out by an elimination diet trial of 8– during the rainy season and winter, was compared using 12 weeks. No concurrent anti-inflammatory, antihista- Fisher’s exact test. The relationship among ASIS results mine or antibacterial/antifungal treatments were allowed for different allergens was determined using Pearson’scor- during the elimination diet trial or 4 weeks prior to relation coefficient (r). A P-value < 0.05 was considered serum collection for ASIS. statistically significant.

Abbreviations Allergen-specific IgE serology (ASIS) AD: Atopic dermatitis; ASIS: Allergen-specific IgE serology; CAD: Canine At least 5 mL of serum sample was collected from each atopic dermatitis; IDT: Intradermal skin tests; IgE: Immunoglobulin E dog by cephalic venipuncture and dogs were returned to Acknowledgements the owner after blood collections. All serum samples were The authors would like to thank all staff at the Dermatology unit, Kasetsart submitted to Animal Allergy Lab, Heska’s International University Veterinary Teaching Hospital, Bangkok, and the owners of the dogs Lab Partners in Singapore, for measurement of allergen- that participated in this study. Vet Diags Co., Ltd, the distributor in Thailand, helped submit serum samples to Animal Allergy Lab, Heska’s International Lab specific IgE (Allercept® allergen specific IgE test, Heska Partners in Singapore. Corp., Singapore). The Asian panel was categorized into 7 groups, including indoor and outdoor allergens and fleas Authors’ contributions SC developed the concept, designed the study, performed the experiment, (Table 1). The indoor allergens included were house dust performed statistical analysis, and wrote the manuscript. NT designed the mites (Dermatophagoides farinae and Blomia tropicalis), study, performed statistical analysis, and revised the manuscript. All authors storage mites (Tyrophagus putrescentiae), and flour mites contributed to the drafting and revision of the manuscript. All authors read (Acarus siro). The outdoor allergens included were and approved the final manuscript. Bermuda grass (Cynodon dactylon), Bahia grass (Paspa- Funding lum notatum), Johnson grass (Sorghum halepense), The present study was financially supported by the Faculty of Veterinary meadow fescue (Festuca pratensis), Timothy grass Medicine (start-up research fund to SC), Kasetsart University. (Phleum pratense), red/sheep sorrel (Rumex acetosella), Availability of data and materials lamb’squarter(Chenopodium album), Russian thistle The data used and/or analyzed in the present study are available from the (Salsola kali), careless weed (Amaranthus hybridus), corresponding author on reasonable request. cocklebur (Xanthium strumarium), marsh elder (Cycla- Ethics approval and consent to participate chaena xanthiifolia), common and giant ragweed (Ambro- The protocol was approved by the Kasetsart University Institutional Animal sia artemisiifolia and A. trifida), English plantain Care and Use Committee and by the Ethical Review Board of the Office of National Research Council of Thailand (NRCT license U1-08491-2562). In- (Plantago lanceolata), mugwort (Artemisia vulgaris), formed written consent was obtained from all dog owners and the experi- paperbark tree (Maleleuca quinquenervia), white mulberry ment complied with the Kasetsart University Institutional Animal Care and (Morus alba), queen and oil palms (Arecastrum romanzof- Use Standards. fianum and Elaeis guineensis), and white oak (Quercus Consent for publication alba). Yeast (Malassezia pachydermatis) and fleas (flea Not applicable. saliva), commonly related to CAD, were also included in Competing interests the analysis. For further information regarding the identi- The authors declare that they have no competing interests. fication of plant materials as well as the acquisition of allergens, please visit the company website (www.heska. Author details 1Department of Companion Animal Clinical Sciences, Faculty of Veterinary com). Based on the concentrations of IgE measured, re- Medicine, Kasetsart University, 10900 Bangkok, Thailand. 2Dermatology Unit, sults were stratified into one of four classes: 0 = no Kasetsart University Veterinary Teaching Hospital, 10900 Bangkok, Thailand. Chermprapai and Thengchaisri BMC Veterinary Research (2020) 16:475 Page 7 of 7

Received: 2 October 2020 Accepted: 19 November 2020 23. Salzmann CA, Olivry TJM, Nielsen DM, Paps JS, Harris TL, Olby NJ. Genome- wide linkage study of atopic dermatitis in West Highland White Terriers. BMC Genet. 2011;12:37. 24. Wood SH, Ollier WE, Nuttall T, McEwan NA, Carter SD. Despite identifying References some shared gene associations with human atopic dermatitis the use of 1. Halliwell R. Revised nomenclature for veterinary allergy. Vet Immunol multiple dog breeds from various locations limits detection of gene Immunopathol. 2006;114:207–8. associations in canine atopic dermatitis. Vet Immunol Immunopathol. 2010; – 2. Chermprapai S, Broere F, Gooris G, Schlotter YM, Rutten VPMG, Bouwstra JA. 138:193 7. Altered lipid properties of the stratum corneum in Canine Atopic Dermatitis. 25. Marsella R. Hypersensitivity disorders. In: Miller WH, Griffin CE, Campbell KL, ’ Biochim Biophys Acta - Biomembr. 2018;1860:526–33. Muller GH, editors. Muller and Kirk s Small Animal Dermatology7: Muller and ’ – 3. Pucheu-Haston CM, Bizikova P, Marsella R, Santoro D, Nuttall T, Eisenschenk Kirks Small Animal Dermatology. St. Louis: Elsevier/Mosby; 2013. pp. 363 431. MN. Review: Lymphocytes, cytokines, chemokines and the T-helper 1-T- 26. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: helper 2 balance in canine atopic dermatitis. Vet Dermatol. 2015;26:124-e32. 2010 clinical practice guidelines from the International Task Force on – 4. Chermprapai S, Ederveen THA, Broere F, et al. The bacterial and fungal Canine Atopic Dermatitis. Vet Dermatol. 2010;21:233 48. microbiome of the skin of healthy dogs and dogs with atopic dermatitis 27. Stedman K, Lee K, Hunter S, Rivoire B, McCall C, Wassom D. Measurement of and the impact of topical antimicrobial therapy, an exploratory study. Vet canine IgE using the alpha chain of the human high affinity IgE receptor. – Microbiol. 2019;229:90–9. Vet Immunol Immunopathol. 2001;78:349 55. 5. Hillier A, DeBoer DJ. The ACVD task force on canine atopic dermatitis (XVII): 28. Lee KW, Blankenship KD, McCurry ZM, Esch RE, DeBoer DJ, Marsella R. intradermal testing. Vet Immunol Immunopathol. 2001;81:289–304. Performance characteristics of a monoclonal antibody cocktail-based ELISA for detection of allergen-specific IgE in dogs and comparison with a high 6. Plant JD, Neradelik MB, Polissar NL, Fadok VA, Scott BA. Agreement between affinity IgE receptor-based ELISA. Vet Dermatol. 2009;20:157–64. allergen-specific IgE assays and ensuing immunotherapy recommendations 29. DeBoer DJ, Hillier A. The ACVD task force on canine atopic dermatitis (XVI): from four commercial laboratories in the USA. Vet Dermatol. 2014;25:15-e6. laboratory evaluation of dogs with atopic dermatitis with serum-based 7. Hensel P, Santoro D, Favrot C, Hill P, Griffin C. Canine atopic dermatitis: “allergy” tests. Vet Immunol Immunopathol. 2001;81:277–87. detailed guidelines for diagnosis and allergen identification. BMC Vet Res. 30. Thom N, Favrot C, Failing K, Mueller RS, Neiger R, Linek M. Intra- and 2015;11:195–6. interlaboratory variability of allergen-specific IgE levels in atopic dogs in 8. Neuber A, Nuttall T. Allergy testing. In: Neuber A, Nuttall T, editors. three different laboratories using the Fc- e receptor testing. Vet Immunol Diagnostic Techniques in Veterinary Dermatology. Hoboken: Wiley; 2017. p. Immunopathol. 2010;133:183–9. 125–58. 31. Saridomichelakis MN, Marsella R, Lee KW, Esch RE, Farmaki R, Koutinas AF. 9. Chanthick C, Anaman S, Buathet K. The prevalence of positive intradermal Assessment of cross-reactivity among five species of house dust and allergy tests in 114 dogs with atopic dermatitis in the Bangkok metropolis, storage mites. Vet Dermatol. 2008;19:67–76. Thailand. Vet Immunol Immunopathol. 2008;126:256–62. 32. Foster AP, Littlewood JD, Webb P, Wood JLN, Rogers K, Shaw SE. 10. Bizikova P, Pucheu-Haston CM, Eisenschenk MN, Marsella R, Nuttall T, Comparison of intradermal and serum testing for allergen-specific IgE using Santoro D. Review. Role of genetics and the environment in the aFcεRIα-based assay in atopic dogs in the UK. Vet Immunol Immunopathol. pathogenesis of canine atopic dermatitis. Vet Dermatol. 2015;26:95-e26. 2003;93:51–60. 11. Bizikova P, Santoro D, Marsella R, Nuttall T, Eisenschenk MNC, Pucheu- 33. Ginel PJ, Riaño C, Lucena R. Evaluation of a commercial ELISA test for the Haston CM. Review: Clinical and histological manifestations of canine atopic detection of allergen-specific IgE antibodies in atopic dogs. Zentralbl dermatitis. Vet Dermatol. 2015;26:79-e24. Veterinarmed B. 1998;45:421–5. 12. Bjelland AA, Dolva FL, Nødtvedt A, Sævik BK. Prevalence of and risk factors 34. Codner EC, Lessard P. Comparison of intradermal allergy test and enzyme- for increased serum levels of allergen-specific IgE in a population of linked immunosorbent assay in dogs with allergic skin disease. J Am Vet Norwegian dogs. Acta Vet Scand. 2014;56:81. Med Assoc. 1993;202:739–43. 13. Jang H-M, Yeo G-S, Kim J-H, et al. Prevalence of serum allergen-specific 35. Olivry T, Jackson HA, Murphy KM, Tater KC, Roberts M. Evaluation of a point- immunoglobulin E for canine atopic dermatitis in Korea. J Biomed Res. of-care immunodot assay for predicting results of allergen-specific – 2014;15:162 9. intradermal and immunoglobulin E serological tests. Vet Dermatol. 2005;16: 14. Caraballo L, Zakzuk J, Lee BW, et al. Particularities of allergy in the Tropics. 117–20. World Allergy Organ J. 2016;9:20. 36. Olivry T, Saridomichelakis M, (ICADA) IC on AD of A. Evidence-based 15. Loo YY, Billa L, Singh A. Effect of climate change on seasonal monsoon in guidelines for anti-allergic drug withdrawal times before allergen-specific Asia and its impact on the variability of monsoon rainfall in Southeast Asia. intradermal and IgE serological tests in dogs. Vet Dermatol 2013;24:225-e49. – Geosci Front. 2015;6:817 23. 37. Randall A, Hillier A, Cole LK, Kwochka KW, Needham G, Wassom DL. 16. Tarpataki N, Papa K, Reiczigel J, Vajdovich P, Vorosi K. Prevalence and Quantitation of house dust mites and house dust mite allergens in the features of canine atopic dermatitis in Hungary. Acta Vet Hung. 2006;54: microenvironment of dogs. Am J Vet Res. 2003;64:1301–9. – 353 66. 38. Nuttall TJ, Hill PB, Bensignor E, Willemse T. House dust and forage mite 17. Zur G, Ihrke PJ, White SD, Kass PH. Canine atopic dermatitis: a retrospective allergens and their role in human and canine atopic dermatitis. Vet study of 266 cases examined at the University of California, Davis, 1992– Dermatol. 2006;17:223–35. 1998. Part I. Clinical features and allergy testing results. Vet Dermatol. 2002; 39. Sævik BK, Ulstein TL, Larsen HJS. Evaluation of a commercially available 13:89–102. enzyme-linked immunosorbent assay for the detection of allergen-specific 18. Favrot C, Steffan J, Seewald W, Picco F. A prospective study on the clinical IgE antibodies in dogs. Res Vet Sci. 2003;74:37–45. features of chronic canine atopic dermatitis and its diagnosis. Vet Dermatol. 2010;21:23–31. 19. Barker JNWN, Palmer CNA, Zhao Y, et al. Null Mutations in the Filaggrin Publisher’sNote Gene (FLG) Determine Major Susceptibility to Early-Onset Atopic Dermatitis Springer Nature remains neutral with regard to jurisdictional claims in that Persists into Adulthood. J Invest Dermatol. 2007;127:564–7. published maps and institutional affiliations. 20. Sugiura H, Ebise H, Tazawa T, et al. Large-scale DNA microarray analysis of atopic skin lesions shows overexpression of an epidermal differentiation gene cluster in the alternative pathway and lack of protective gene expression in the cornified envelope. Br J Dermatol. 2005;152:146–9. 21. Sousa CA, Marsella R. The ACVD task force on canine atopic dermatitis (II): genetic factors. Vet Immunol Immunopathol. 2001;81:153–7. 22. Egli KS, Schiessl B, Roosje PJ, et al. Evaluation of the usefulness of sensitization to aeroallergens as a model for canine atopic dermatitis in genetically predisposed Beagles. Am J Vet Res. 2002;63:1329–36.